1. Field of Invention
The present invention relates to a tandem mass spectrum analysis device and a tandem mass spectrum analysis method, and more particularly, to a multi-mode analysis device and method for realizing single-stage to multi-stage mass spectrometry with a quadrupole mass filter combined with an ion trap.
2. Related Art
Chromatography-mass spectrometer, especially gas chromatography-mass spectrometer is playing an increasingly important role with rising demand in analysis field as industrial production, environmental monitoring. New technologies are emerging in all the sub-field of chromatography, mass spectrometry, and their interfaces, and help to increase the kinds of instrument. In terms of the mass spectrometry, the mass spectrometer for gas chromatography connection has been developed from the initial magnetic fan mass spectrometer to the single quadrupole mass spectrometer, ion trap mass spectrometer, and time-of-flight mass spectrometer that are widely used at present. The price of the instrument decreases significantly, and the analysis efficiency is increased. To effectively resolve some complex unknown samples, a tandem mass spectrometer is developed to make tandem mass spectrometry (MSn) for separated products of the gas chromatography. The tandem mass spectrometer combined with the gas chromatography is mainly classified in an ion trap mass spectrometer and a triple quadrupole mass spectrometer. The triple quadrupole mass spectrometer adds an ion collision chamber and a second quadrupole analyzer after a first quadrupole analyzer. The first quadrupole analyzer selects one of ions (possibly caused by poor separation of previous chromatography) or multiple fragment ions generated by the ion source and enables the selected ion to enter the collision chamber through the analyzer to perform collision dissociation with neutral gas atoms, and fragment product ions thereof enter the second quadrupole analyzer for analysis, so as to obtain a second-stage mass spectrum. When the chromatography has complex composition co-eluting, the second-stage mass spectrum has higher signal-to-background ratio and quantitative accuracy than the single-stage mass spectrum, and structure information of the analyzed ions can also be obtained.
When people want to further resolve the structure of the collision product ions, the demand of MSn for mass spectra of more than three stages is put forward, the triple quadrupole analyzer is unable to do that, but the ion trap good at MSn (n>=3) exhibits its superiority.
Early in the 1980s, the Finnigan Company in U.S. produced a chromatography-mass spectrometer like a gas chromatography three-dimensional (3D) ion trap detector, which can make tandem mass spectrometry for multiple times, has a low price, and is widely used until today. However, a 3D quadrupole ion trap has the following problems in the combination with the gas chromatography:
1. Before precursor ion selection and mass scanning, the 3D quadrupole ion trap needs to cool and gather all the ions in a small area of the ion trap center, due to charge interactions among the ions, if the ion density is high, the ion resonance ejection process may be affected by the ion space charge, the resolution becomes poor, and the peak shifts. In other words, the space charge effect greatly limits the number of ions allowed by each operation. Since the number of the ions analyzed each time is limited (generally several hundreds to tens of thousands, depending on the mass-to-charge ratio range and the scan speed), this influences the dynamic range of the instrument analysis.
2. The gas chromatography-mass spectrometer widely uses an electron bombardment ion source (EI). Such an ion source generates a series of fragment ions in the ionization of sample molecules. Determining composition of a compound according to the fragment ion abundance proportional relation has become a standard analysis method. A standard database of thousands of samples has been formed for the most widely used (EI) quadrupole mass spectrometer, but because a longer ion storage time is required for analysis of the quadrupole ion trap, facilitating generation and transformation of fragment ions, resulting in a great difference between the fragment abundance relation in the quadrupole ion trap mass spectra and the fragment abundance relation in the quadrupole mass spectra, and a number of compounds cannot be accurately identified according to the standard database after being analyzed with an ion trap analyzer.
3. When an ion trap is used for tandem mass spectrometry, precursor ions must be excited first to obtain sufficient ionization kinetic energy, and then product ions can be got in collision with the gas molecules. To capture a precursor ion having sufficient kinetic energy in the ion trap, the stability parameter q of the precursor ion must be large enough, so as to obtain a sufficiently deep pseudopotential well. This will result in the lower mass limit of a fragment product ion, that is to say, if the mass of the fragment product ion is less than the lower mass limit corresponding to the q, the product ion cannot be captured by the ion trap, thereby causing ion loss. Generally, the lower mass limit of a product ion is one third of the mass of the precursor ion, which may limit the available mass range of multi-stage mass spectra.
With the invention of a linear ion trap, problems about ion volume and dynamic range of the 3D ion trap have been solved in a large extent. This has been described in U.S. Pat. No. 5,420,425 and No. US19960656954. However, when the linear ion trap is combined with an electron impact ionization source (EI), the cracking form varies greatly as compared with the quadrupole mass filter, which also causes serious problems for database retrieval. A digital wave-driven ion trap (Chinese Patent No. ZL200710045190) can rapidly change the value of q in the collision-induced dissociation (CID) process, which improves the contradictory problem between the product ion lower mass limit and the precursor ion excitation energy to some extent; this has been disclosed in U.S. Pat. No. 7,582,866 and U.S. Pat. No. 6,949,743. However, the methods disclosed cannot really realize the condition of high-energy CID used in the triple quadrupole instrument. Owing to the foregoing ion trap problems, although the linear ion trap has been successfully applied to the liquid chromatography mass spectrometry (LCMS), the linear ion trap has not yet been commercialized in the field of gas chromatography mass spectrometry (GCMS).
Objectives of the present invention are, first, finding a scheme of an instrument that is capable of realizing multi-stage tandem mass spectrometry (three stages or more), has high sensitivity and product ion output efficiency, and maintains higher dynamic ranges of first-stage mass spectra and second-stage mass spectra; and second, integrating two superiorities of the instrument, that is, the advantage of being easy to use database to make mass spectrum retrieval for the EI source fragment ions and the advantage of performing multi-stage tandem mass analysis to determine unknown compounds.